Women with palmoplantar pustulosis have disturbed calcium homeostasis and a high prevalence of diabetes mellitus and psychiatric disorders: a case-control study

Palmoplantar pustulosis is characterized by pustule formation in the acrosyringium. Nearly 50% of palmoplantar pustulosis sera produce immunofluorescence of the palmar papillary endothelium from healthy subjects, but also of the endothelium of normal parathyroid gland. With a case-control design the levels of calcium and parathyroid hormone in serum were measured in 60 women with palmoplantar pustulosis and 154 randomly selected population-based control women. One-third of the controls had been smokers, whereas 95% of the cases were or had been smokers. Mean age-adjusted serum calcium was increased in the patients compared with the controls (2.43 vs 2.36 mmol/l; p<0.0001), whereas the parathyroid hormone concentration was suppressed (23.2 vs 31.1 ng/l; p<0.0001). The plasma levels of parathyroid hormone-related protein were normal in patients but there was a strong expression of this protein in the acrosyringium both in palmoplantar pustulosis and control skin. As even a marginal elevation of serum calcium is associated with an increased risk for diabetes, cardiovascular disease and psychiatric disease, we analysed the risk for these disorders in palmoplantar pustulosis patients compared with that in the control group. Both diabetes mellitus and psychiatric disorders were associated with palmoplantar pustulosis with an odds ratio of 8.7 (95% CI 3.3-22.8) and 5.6 (95% CI 2.2-14.4), respectively. Palmoplantar pustulosis is a complex disease with an increased risk for several non-dermatological disorders. The role of the mildly increased serum calcium for the high risk for diabetes and depression deserves to be studied.     

Plaque psoriasis in patients with palmoplantar pustulosis

This study from the USA, Denmark and Germany looked at how often plaque psoriasis and palmoplantar pustulosis (PPP) occur together. Plaque psoriasis is the commonest form of psoriasis. PPP is a condition where pus-filled spots are seen on the palms and soles, often on skin that is red and scaly like psoriasis. It is not known how PPP is related to psoriasis, if at all. From insurance records in the USA and Germany, and from the Danish National Patient Register, the researchers found approximately 4000 patients diagnosed with PPP. Many of their findings varied strikingly from country to country, as noted in the commentary for this study. For instance, the prevalence of PPP ranged from 0.005% in Denmark to 0.08% in Germany. The presence of plaque psoriasis in PPP patients varied from 14.2% in the Danish patients to 36.4% in Germany and 61.3% in the USA. As regards treatment, patients with PPP and plaque psoriasis together were more likely to have been prescribed strong steroid creams, ointments or gels, especially in the USA and Denmark. More patients with both conditions together were treated with acitretin, methotrexate and biologics in the USA and Denmark, and the differences for treatment with biologics ranged widely: 18.4% of USA patients compared with 8.5% in Denmark and 2.5% in Germany. In comparison with patients with PPP alone, patients who had PPP and plaque psoriasis together were more likely to have joint disease related to psoriasis, and this was roughly the same in all three countries.     

Clinical and epidemiological comparison of patients affected by palmoplantar plaque psoriasis and palmoplantar pustulosis: a case series study

Summary Background In 2007 the International Psoriasis Council proposed that palmoplantar pustulosis (PPP) should be considered a separate condition from psoriasis, despite the presence of certain phenotypes common in both diseases. Objectives To describe and compare demographic and clinical characteristics among patients with PPP and palmoplantar plaque psoriasis. Methods This was a retrospective case series study from 2005 to 2010. The following data were obtained: age, sex, family history, smoking habits, nail involvement, joint involvement, disease duration, lesion morphology (plaque or pustular), histological diagnosis, comorbidities, and Physician’s Global Assessment (PGA) score for extrapalmoplantar lesions. The sample size calculation indicated that 80 patients, 40 patients for each group (palmoplantar plaque psoriasis and PPP) were needed to see clinically relevant differences between groups. Results Ninety patients were selected, 51 with palmoplantar plaque psoriasis and 39 with PPP. No statistically significant differences were registered between patients affected by PPP and palmoplantar plaque psoriasis as regards age at onset of the disease (48 vs. 44 years; P = 0·4), disease duration (6 vs. 10 years; P = 0·1), family history of psoriasis (28% vs. 33%; P = 0·7), concomitant arthritis (26% vs. 25%; P = 1·0), or smoking habits (54% vs. 41%; P = 0·2). We observed a female predominance (P = 0·01) and a lesser frequency of nail involvement (P = 0·03) in patients affected by PPP. Conclusions Our data suggest a close relationship between PPP and psoriasis. The existing data concerning epidemiology, clinical presentation, genetics, histopathology and pathogenesis do not permit a clear distinction between these two entities, which seem to coincide in many aspects. PPP appears to have a marked predilection among female smokers.     

Factors associated with palmoplantar or plantar pompholyx: a case-control study

BACKGROUND: Disydrosis or pompholyx is a chronic and recurrent form of dermatosis that poses a number of therapeutic issues. The etiopathology of the condition is unclear. The aim of this study was to identify factors associated with the palmoplantar and plantar dysidrosis. PATIENTS AND METHODS: This was a prospective case-control study conducted between June 2001 and February 2004 at the University Hospital of Lome (Togo). Each case (palmoplantar or plantar pompholyx) was matched for age (+/- 5 years) and sex with two controls. Examination for tinea pedis was performed in all participants (patients and controls) but mycologic culture alone was done in patients with interdigital-plantar intertrigo. RESULTS: One hundred patients with pompholyx were matched with 200 controls. Mean age was 32.8 +/- 14.8 years in the patient group and 31.4 +/- 14.8 years in the control group. For univariate analysis, the main factors associated with pompholyx were: personal atopy (OR = 12.6; CI95%: 6.4 - 25.1) and familial atopy (OR = 5.8; CI95%: 3.2 - 10.5); history of eczema (OR = 5.4; CI95%: 2.6 - 11.4); hyperhidrosis (OR=4.5; CI 95%: 5.5 - 40.7), sport (OR = 8.8; CI 95%: 3.9 - 20.8); tinea pedis (OR = 15.6; CI 95%: 7.5 - 32.9). In multivariate analysis, atopy (OR = 10.5; CI95%: 8.4 - 20.8) and tinea pedis (OR = 18; CI95%: 10.5 - 25.2) were the only factors associated with pompholyx. Trichophyton rubrum was the most common etiology of tinea pedis in both patients and controls.DISCUSSION: The results of this study show atopy and tinea pedis as factors statistically associated with palmoplantar or plantar pompholyx. However, only cohort studies can determine the precise causal relationship between tinea pedis and pompholyx.     

Clinical characteristics and associations of palmoplantar pustulosis: an observational study

BackgroundPalmoplantar pustulosis is a chronic and relapsing disease of the palms and soles, which is characterized by scattered clusters of pinhead-sized, sterile pustules.ObjectiveThe aim of the present study was to determine demographic features, co-morbidities, and relation of palmoplantar pustulosis with psoriasis.MethodsA total of 48 patients (M/F: 15/33) were enrolled in the present study. A detailed history regarding age of onset, palmoplantar pustulosis duration, number of recurrences, personal and family history of psoriasis, accompanying arthritis, sternoclavicular tenderness, dental fillings, smoking status, and autoimmune disease was obtained; thorough dermatological examination was carried out. Patch testing results and laboratory investigations for thyroid autoimmunity were recorded.ResultsThirty-five of 48 patients (72.9%) were current smokers. Twenty of the 48 patients (41.7%) had dental fillings. There was not any significant correlation between palmoplantar pustulosis duration and dental filling duration (p = 0.170). Psoriasis was not detected in any patients either in history or in dermatological examination. Nail involvement and joint complaints were observed in seven of 48 patients (14%) and in nine of 48 patients (18%), respectively. Autoimmune thyroiditis was observed in four of 48 patients (12%). Patients with patch testing positivity (12.5% of patients, M/F: 1/5) had no considerable association for history of external contact with these materials.Study limitationsRetrospective analysis.ConclusionPalmoplantar pustulosis appears to be a distinct entity from psoriasis. Routine thyroid functions test could be analyzed, but patch testing is not required in patients with palmoplantar pustulosis. Also, patients with palmoplantar pustulosis must be evaluated for musculoskeletal symptoms and signs.     

Association between palmoplantar pustulosis and cigarette smoking in Brazil: a case–control study

Background  Palmoplantar pustulosis (PPP) discloses some differences compared to vulgar psoriasis (PV) in terms of age of onset, female predominance and low occurrence of psoriasis lesions elsewhere. Cigarette smoking has been associated to PPP in international studies; nevertheless, these studies were never performed among Brazilian.
Objectives  To compare prevalence of smoking among PPP, PV and other dermatologic patients (NPD).
Methods  Case–control study involving 25 PPP patients from a reference psoriasis centre. Two control groups were matched according to gender and age: 50 patients with PV and 50 NPD. Confounders were adjusted by conditional multiple logistic regression.
Results  Among cases, 84.0% were female and PPP age of disease onset (41.4 years) was greater than PV (34.5 years). Prevalence of ever smoking was higher among cases (92.0%) than PV (52.0%) and NPD (30.0%). Adjusted odds ratio of PPP ever smoking compared to PV and NPD was 9.5 and 36.2, respectively. All smokers reported the onset of their habit before the development of PPP.
Conclusions  There was significant association between PPP and smoking. However, the impact of giving it up in the clinical course of the disease remains to be established.     

Expression of nicotinic receptors in the skin of patients with palmoplantar pustulosis

BACKGROUND: A suggested role for nicotine in the pathogenesis of palmoplantar pustulosis (PPP) has been discussed. The target for the inflammation in PPP is the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine receptors (nAChRs) and can influence a variety of cellular functions. OBJECTIVES: To study the alpha 3- and alpha 7-nAChR expression in palmar skin of patients with PPP in comparison with that in healthy smoking and non-smoking controls. METHODS: Biopsies from 20 patients with PPP, seven healthy smokers and eight healthy non-smokers were studied by immunohistochemistry with a monoclonal anti-alpha 3 and a polyclonal anti-alpha 7 antibody. RESULTS: In healthy controls both nAChR subtypes showed stronger immunoreactivity in the eccrine glands and ducts than in the epidermis. The papillary endothelium was positive for both subtypes. Epidermal alpha 3 staining was stronger and that of the coil and dermal ducts weaker in healthy smokers than in healthy non-smokers. In involved PPP skin, granulocytes displayed strong alpha 3 immunoreactivity. The normal epidermal alpha 7 staining pattern was abolished in PPP skin and was replaced by strong mesh-like surface staining, most markedly adjacent to the acrosyringium, which in controls was intensely alpha 7 positive at this level. Endothelial alpha 7 staining was stronger in PPP skin than in the controls. CONCLUSIONS: Smoking can influence nAChR expression. The altered nAChR staining pattern in PPP skin may indicate a possible role for nicotine in the pathogenesis of PPP. We hypothesize that there is an abnormal response to nicotine in patients with PPP, resulting in inflammation.     

Skin nerve fibres and their contacts with mast cells in patients with palmoplantar pustulosis

Abstract Patients with palmoplantar pustulosis (PPP) frequently report that stress worsens their condition. A study was therefore made of the distribution and number of nerve fibres positive for protein gene product (PGP) 9.5 (a general nerve marker) and nerve fibres with substance P- and calcitonin gene-related peptide-like immunoreactivity in involved skin from patients with PPP and in skin from healthy controls. The number of mast cells in the papillary dermis was larger (P = 0.0003) in lesional palmar PPP skin than in control skin, and the number of contacts between mast cells and nerve fibres was significantly larger (P = 0.02) in PPP skin than in control skin. Image analysis of the nerve fibres around the sweat glands showed that the positively stained area as a percentage of the total area of the sweat gland (coil + surrounding nerves) was significantly lower in PPP skin (P = 0.0006). Furthermore, the nerves seemed to be fragmented. Neutrophils within and below the pustules and in the papillary dermis showed positive substance P staining. The increased number of contacts between nerves and mast cells in PPP skin and the intense substance P-like immunoreactivity of the neutrophils indicate that neuromediation may influence the inflammation in PPP, whereas the destruction of the nerve fibres around the sweat glands might be a result of the inflammation. Received: 8 October 1999 / Revised: 25 January 2000 / Accepted: 27 January 2000     

Production of interleukin-2 and interleukin-2 inhibitor in patients with palmoplantar pustulosis

We studied production of interleukin-2 (IL-2) and IL-2 inhibitor from peripheral blood of patients with palmoplantar pustulosis (PPP). Nineteen patients were divided into two groups: those with and those without arthro-osteitis. Although IL-2 production in both groups of patients was within normal limits, those with arthro-osteitis showed greater fluctuation in relation to the disease activity. The IL-2 production of five PPP patients with arthro-osteitis was greatly enhanced in the inactive stage compared with the active stage. Sera from two patients treated with a combination of etretinate and colchicine contained extremely low levels of IL-2 inhibitory activity. The increased IL-2 production in the inactive stage may be due in part to the depletion of IL-2 inhibitor-producing cells by the treatment.